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Macrophages are accessory cells that are vulnerable to infection by HIV-1. HTLV-IIIB, a lymphotropic strain of HIV, infects macrophages poorly resulting in either no or low levels of virus expression compared to high levels of productive infection after exposure of macrophages to the monocytotropic HIV strain Ada-M. Whether this results in an impaired ability of HTLV-IIIB-exposed macrophages to initiate protective cytotoxic T lymphocyte (CTL) immune responses against these strains is not well defined. We investigated the ability of monocyte-derived macrophages (MDM) exposed to lymphotropic and monocytotropic HIV strains to initiate primary CTL responses in vitro. MDM exposed to HTLV-IIIB induced a specific primary CTL response that was comparable to MDM exposed to the monocytotropic strain Ada-M despite marked differences in productive HIV infection in MDM between the two strains. CTL generated in this model were MHC-restricted, strain-specific, and CD8+. These data demonstrate that high levels of productive HIV infection in accessory cells are not a prerequisite for the generation of a primary CTL response, suggesting a novel immunologic interaction between MDM and lymphotropic HIV strains.

HIV-infected individuals frequently develop Mycobacterium tuberculosis (MTB) infection. Alveolar macrophages (AM) are the initial host defense against this organism. We measured MTB growth in AM from normal and HIV-infected subjects after in vitro exposure. Intracellular growth of MTB was reduced in AM from HIV-infected subjects compared with normal macrophages. This was confined to subjects with CD4 counts greater than 200/microl. Growth of avirulent mycobacteria in HIV macrophages was significantly less than virulent MTB. Because avirulent MTB is more sensitive to tumor necrosis factor-alpha (TNF-alpha), we examined the relationship between cytokine secretion and mycobacterial growth. Higher AM spontaneous TNF-alpha secretion was associated with reduced MTB growth in normal AM. This relationship was not seen in HIV-infected subjects, suggesting that other factors contributed to mycobacteria resistance. Mycobacteria-induced TNF-alpha secretion was inversely associated with growth in normal AM but not in HIV-infected subjects. Finally, binding and internalization of MTB was augmented in HIV macrophages compared with normal, demonstrating that reduced intracellular MTB growth was not due to impaired phagocytosis. In conclusion, the increased incidence of MTB infection in HIV-infected subjects does not appear to be due to a defect in macrophage innate immunity.

Lymphocytic alveolitis portends a poor prognosis in human immunodeficiency virus (HIV)-infected subjects. Because alveolar lymphocytes consist predominantly of HIV-specific CD8(+) cytotoxic T lymphocytes (CTL), they could represent an appropriate immune response to infected cells in the lung, and be a surrogate marker for a high pulmonary viral burden. We assessed long-term outcome in a cohort of asymptomatic HIV-infected subjects who underwent bronchoscopy between 1990 and 1993 and had bronchoalveolar lavage fluid (BALF) available for determination of viral load by reverse transcription-polymerase chain reaction. The ability to detect HIV in BALF increased with disease progression. Lymphocytic alveolitis, although present at all stages of HIV infection, was most pronounced in patients with middle stage disease. The HIV viral load as measured by bronchoalveolar lavage correlated with the percentage of alveolar lymphocytes in patients with peripheral blood CD4(+) cell counts above 200/microliter. Including patients with CD4(+) cell counts < 200/microliter weakened this correlation, possibly because of replacement of CD8(+) CTL by CD8(+) suppressor cells in advanced disease. Free virus in BALF was a stronger predictor of HIV disease progression than was lymphocytic alveolitis. These data suggest that lymphocytic alveolitis in HIV-infected subjects occurs in response to viral antigens in the lung and that the poor prognosis associated with lymphocytic alveolitis reflects a high pulmonary viral burden.

Human immunodeficiency virus (HIV)-infected patients in Malawi have a high incidence of pneumococcal pneumonia. Since IgG2 is known to be protective against Streptococcus pneumoniae, we measured pneumococcal-specific IgG (IgG-pn), IgG1 (IgG1-pn), and IgG2 (IgG2-pn) in bronchoalveolar lavage (BAL) fluid to see if a quantitative deficit might explain this observation. IgG-pn, IgG1-pn, and IgG2-pn were measured to determine if there was a change in the ratio of immunoglobulin isoforms. Fifty-two BAL samples were collected from 26 HIV-infected HAART-naive Malawi patients and 26 HIV-negative volunteers. IgG-pn, IgG1-pn, and IgG2-pn were determined using sandwich ELISA techniques. ELISA wells were coated with pneumococcal vaccine (Pneumovax 23). Biotinylated IgG, IgG1, and IgG2 were used as the secondary antibodies. Data are expressed as ng/mL BAL ± SEM. Total IgG-pn was elevated in HIV+ patientss compared with HIV− patients (p = .0098), as were IgG2-pn (p = .0002) and IgG1 (p = .0067). HIV-infected patients did not have a statistically significant difference in IgG1/IgG2 ratio compared with HIV-negative patients (p = .3804). In conclusion, despite the high incidence of invasive pneumococcal disease in Malawi, HIV-infected Malawians had higher total IgG-pn-, IgG1-pn-, and IgG2-pn-specific antibodies in BAL than uninfected subjects. We speculate that this may be related to elevated proinflammatory cytokines in HIV BAL, including IFN-γ, which is known to stimulate IgG2 production in particular. These results suggest that the high incidence of pneumococcal pneumonia in Malawi is not due to a quantitative deficit in IgG levels but rather points to potential functional antibody defects.

Background and Objective The incidence of invasive pneumococcal disease among HIV-infected persons has declined in the post HAART era. Changes in the humoral immune responses have been implicated in this change. It has already been shown that HAART is associated with a decline in BAL total IgG and IgM concentrations and a decrease in BAL pneumococcal-specific IgG concentrations. We measured total and pneumococcal-specific IgA concentrations in BAL of 24 HIV-infected patients before and at 4 and 24 weeks after initiation of HAART, anticipating a similar response. Methods BAL pneumococcal-specific IgA levels were measured using ELISA. The IgA concentrations were corrected for dilution by determining epithelial lining fluid (ELF) using the urea dilution technique. Results Data expressed as mean ± SEM μg IgA/mL ELF (* p value ≥ .05). Total and pneumococcal-specific IgA levels did not change after initiation of HAART. No change was detected in the levels of pneumococcal-specific IgA when expressed as a percentage of total IgA. No significant correlation was found between BAL IL-6 and IgA concentration or BAL percentage lymphocytes and IgA concentrations. Conclusion HAART is not associated with significant changes in total or pneumococcal-specific IgA concentrations in the distal respiratory tract. We speculate that this reflects the more dominant role of IgG in protection of the alveolar space against bacterial pathogens.

Background and Objective Mycobacterium tuberculosis (MTB) is a common cause of pulmonary disease in HIV-infected patients. Normal alveolar macrophages (AM) phagocytize MTB and are then activated by cytokines to kill ingested MTB. We have previously shown that HIV alveolar AM are intrinsically resistant to MTB infection compared to normal AM, likely due to an AM-activating factor secreted by alveolar T cells. In this work, we examined the ability of concentrated BAL from HIV-infected subjects to activate AM to kill MTB. Methods BAL from HIV-infected subjects before and after starting antiretroviral therapy were concentrated 5 times using 10 kD spin columns and then cultured with normal AM for 24 hours. Virulent and avirulent MTB at an MOI of 1:1 was then added and subsequent infection determined using a BACTEC methodology. BAL cytokine concentrations were measured using a cytometric bead array assay system. Time to initial and maximal infection of the AM by MTB was assessed. Results Virulent and avirulent MTB grew equally well in AM not treated with HIV BAL. However, pretreatment with HIV BAL significantly delayed AM infection (both initial and maximal) by avirulent MTB compared to virulent MTB (initial infection: 12.2 ± 0.3 days vs 9.8 ± 0.3 days, p

Invasive pneumococcal disease is a significant cause of morbidity and mortality in the HIV-infected Malawian population despite high concentrations of anti-pneumococcal antibody concentrations in bronchoalveolar lavage (BAL). Thus we undertook this study to assess the opsonic function of the antibody. 23 HIV-infected and 26 uninfected subjects underwent bronchoscopy with BAL. IgG was purified from BAL on a protein G column. Serotype 1 anti-pneumoccal specific IgG antibody was determined by ELISA. The ability of purified IgG to bind to serotype 1 pneumococci was determined by mixing pneumococcus, purified IgG, and FITC-labelled anti-IgG and analysis by flow cytometry. The ability of FITC-labelled pneumococci coated with purified IgG to bind to monocyte monolayers was determined in a luminometer before and after quenching surface bound FITC with trypan blue. (Table) Serum and BAL from HIV-infected subjects contained significantly more serotype type 1 specific anti-pneumococcal IgG than normal serum and BAL. Despite this, when equal amounts of purified IgG were added to serotype 1 pneumococci significantly less antibody bound to the organism, both as a percent of pneumococci stained (61 ± 11.8% vs 53 ± 6.6%, p = .001) and as a fluorescent geometric mean indicating intensity of binding. Finally, when serotype 1 specific pneumococci were pretreated with equal amounts of purified BAL IgG, less organisms bound to monocytes after opsonization with HIV IgG compared to normal IgG (60 ± 14% vs 67 ± 14%, p = 0.065). Similar amounts of bound organisms were ingested. These studies suggest that although HIV infection is associated with increased anti-pneumococcal antibody secretion, the antibody demonstrates a significant impairment in its ability to opsonize bacteria. These results may explain the increased susceptibility of HIV-infected subjects to pneumococcal infections. This abstract is funded by NIH RO1 HL62058 (H.L.T.) and the Wellcome Trust (S.B.G.).

(1980). Rosa Luxemburg and the accumulation of capital. Critique: Vol. 12, No. 1, pp. 81-96.

Rats were trained on fixed ratio (FR) schedules requiring either 5 or 10 leverpresses to produce reinforcement and an intertrial interval (ITI). Half of the Ss at each ratio requirement were extinguished on an FR 5 and half on an FR 10 schedule of ITI presentation. Fewer foodcup approaches were made on the FR 10 than on the FR 5 extinction schedule, regardless of acquisition FR. Leverpresses per approach were fewer on the FR 5 than on the FR 10 extinction schedule and were fewer following FR 5 than following FR 10 acquisition. Data suggested the existence of interoceptive as well as exteroceptive stimulus control of foodcup approach and were discussed in terms of their implications for a response-unit account of extinction.

(1982). Leon Trotsky on the problems of the smychka and forced collectivization. Critique: Vol. 13, Economics of the left opposition, pp. 55-68.

(1975). Preobrazhensky and the theory of the transition period. Soviet Studies: Vol. 27, No. 2, pp. 196-219.

At the end of 1922 Lenin was prompted by a sudden deterioration of his health to write his political testament. In it he declared that although Nikolai Bukharin was "the biggest and most valuable theoretician of the party," nevertheless "his theoretical views can only with the greatest doubt be regarded as fully Marxist, for there is something scholastic in him (he has never learned, and I think has never fully understood dialectics)."i Stephen E. Cohen's recent study2 has provided a comprehensive history of Bukharin's political career, making it appropriate now to explore the meaning of Lenin's comment and thus to assess the significance of Bukharin as a Marxist theorist. In the present essay, following Lenin's criticism, an effort will be made to interpret Bukharin's major theoretical writings from a methodological point of view. This approach, beginning with a brief exposition of Lenin's own use of the dialectical method, will make it possible to compare the works of the two men on several common themes and thus to determine the theoretical and practical origins of their differences. According to Lenin both the material world and all social existence are characterized by dialectical contradictions. "The identity of opposites," he wrote in his Philosophical Notebooks, "... is the recognition (discovery) of the contradictory, mutually exclusive, opposite tendencies in all phenomena ..."" While Lenin suggested that the concept of the identity of opposites expressed "the essence of dialectics,"4 in his investigation of any concrete social totality he invariably undertook a much more subtle and far-reaching study than this summary phrase might suggest. At a time when most other prominent Marxists, including Kautsky, Luxemburg, and Plekhanov, oriented their theoretical writings mainly on the principal contradiction of capitalist society that between the proletariat and the bourgeoisie, as social classes Lenin held that society could only be properly understood as a complex of heterogeneous relations. The principal contradiction, in other words, only assumed practical political significance through a careful analysis of its numerous specific and particular manifestations. As Lenin remarked: "Dialectics calls for a many-sided investigation into a given social phenomenon in its development, and [only then] for the external and seeming to be reduced to the fundamental motive forces, to the development of the class struggle. "5 To focus attention exclusively upon the principal contradiction was, in Lenin's

A highly original and controversial examination of events in Soviet Russia from 1917 to 1927 in which Professor Day challenges both the standard Trotskyite and Stalinist interpretations of the period. At the same time he rejects the traditional emphasis on Trotsky's concept of Permanent Revolution and argues that a Marxist theorist is essential. Professor Day concentrates upon the economic implications of revolutionary Russia's isolation from Europe. How to build socialism - in a backward, war-ravaged society, without aid from the West: this problem lay behind many of the most important political conflicts of Soviet Russia's formative years.